Higher Rates of Bleeding and Thromboembolism When Dabigatran Used as Periprocedural Anticoagulation During AF Ablation

　　Lakkireddy及同事研究了达比加群酯作为心房颤动（AF）消融围手术期抗凝药物的安全性和有效性。这是一项病例对照研究，将不间断华法林治疗作为对照。在145对病例中，达比加群酯组中有3例（2.1%）发生血栓栓塞并发症，华法林组中为零。这些结果提示，达比加群酯，至少以这个方案中的用法，不应被用作AF消融的围手术期抗凝药物。

　　J Am Coll Cardiol 2012 59: 1168-1174.

　　点评：达比加群的药代动力学决定其不适合用于围手术期的不间断治疗
　　Roger A. Winkle， M.D   Silicon Valley Cardiology
　　The report by Lakkireddy， et al. describes the use of uninterupted periprocedural dabigatran and compares it to the use of uninterupted warfarin in patients undergoing AF ablation.  This multicenter study noted a significant increase in bleeding and thromboembolic complications for dabigitran compared to warfarin.  The findings of this study show the importance of understanding the pharmacokinetics of an anticoagulant such as dabigitran.  Dabigatran possess several pharmacokinetic properties that are important to its safe periprocedural AF ablaton use. Several aspects of the clinical pharmacology of dabigitran suggest a potential for complications when used in an uninterrupted manner for AF ablations.
　　1.There is an in vitro heparin-dabigatran interaction. Dabigatran potentiates heparin’s antithrombotic properties with a doubling of anticoagulant effect.  The increase of bleeding complications in the report of Lakkireddy， et al. suggests that this interaction occurs in vivo.
　　2.After hip surgery， dabigatran absorption can be both delayed and reduced.  As a result， oral dabigatran may not provide anticoagulation during the immediate postprocedural period.  This could lead to an incease in post-procedural thromboembolic events.  Administration of enoxaparin immediately following ablation will avoid this “anticoagulant lapse” until oral absorption of dabigatran can be assured.
　　3.Dabigatran has no direct antidote， so if bleeding complications occur， they may be more difficult to reverse than those which occur with warfarin anticoagulation.
　　Based on these pharmacokinetic considerations it may not be appropriate to use dabigatran in an uninterrupted manner.  This does not diminish dabigatran’s utility when used in an interrupted manner.  We have reported the safe use of interupted dabigatran and have subsequently extended our experience to more than 400 patients without a single hemorhagic or thromboembolic event.
　　Heparin administration to patients in whom dabigatran has not been fully interrupted might be expected to lead to increased bleeding complications and poor absorption post-ablation might lead to increased thromboembolic events.  While these are very real concerns that need to be addressed， the convenience of oral dabigatran dosing and elimination of warfarin monitoring makes dabigatran and other new oral anticoagulants attractive alternatives to warfarin for AF ablation patients.
　　中文摘要
　　Lakkireddy等的研究描述了在AF患者进行消融时，围手术期不间断应用达比加群，与不间断应用华法林进行了比较。这项多中心研究发现，与华法林相比，达比加群显著增加了出血和血栓栓塞并发症。这些结果说明，理解抗凝药物如达比加群的药代动力学非常重要。达比加群有几项药代动力学特点，对AF消融围手术期的安全使用很重要：（1）肝素与达比加群在体外有相互作用，达比加群加强肝素的抗血栓作用，使抗凝效果增加了一倍。本研究中达比加群出血并发症的增多，表面这种相互作用在体内也能发生。（2）在全髋关节置换术后，达比加群的吸收减慢和减少，可能不能提供足够的术后抗凝效应，导致术后血栓栓塞事件增加。（3）达比加群没有直接的解毒药，出血一旦发生，不易纠正。
　　基于上述药代动力学特征，达比加群可能不适合用于不间断治疗，但这不能减弱其在间断用法的作用，我们之前在超过400例患者间断使用达比加群，没有发生一例出血和血栓栓塞事件。